Low thyroid in pregnancy risks schizophrenia in baby
Study links a mother's untreated low thyroid hormone levels during pregnancy with a 2% increased risk for her child having neurodevelopmental disorders — such as autism, bipolar disorder or schizophrenia.
Hypothyroxinemia, or low thyroid hormone levels, during pregnancy is common in pregnant women. Previous studies have demonstrated the pivotal role exerted by maternal Free thyroxine (free T4) on fetal brain development and the negative impact of hypothyroxinemia on neurobehavioral performance in offspring. Therefore, thyroid levels are monitored in pregnant women. Low levels of free thyroxine in pregnant women can also induce preterm birth, also a risk factor for schizophrenia.
To expand knowledge on the impact of hypothyroxinemia, study leader and senior author Alan Brown PhD, Professor of Psychiatric Epidemiology, Columbia University Medical Center, New York State Psychiatric Institute, and Columbia University's Mailman School of Public Health, examined blood serum samples from a Finnish Maternity Cohort study of thyroxine levels archived from 1,010 mothers of children with schizophrenia and 1,010 matched control mothers.
These blood samples were collected during the first and early second trimesters of pregnancy and are part of a comprehensive Finnish registry of it's population with psychiatric diagnoses. The samples provided information on a per case basis (cognitive disorder or control) among offspring of mothers registering prenatal low thyroid levels.
Researchers found 11.8% of people with schizophrenia were born to a mother with hypothyroxinemia, as compared to 8.6% of people in the study without schizophrenia — a statistically significant finding.
This small difference suggests increased odds for developing schizophrenia in children of mothers with hypothyroxinemia in pregnancy.
The statistical association remained even after adjusting for other variables related to schizophrenia — such as mom's psychiatric history and/or smoking.
David Gyllenberg PhD from the University of Turku, Finland, and first author of the study, was a visiting scholar at Columbia University when much of the research was conducted. He sees the importance of this difference as it "links the finding to an extensive literature on maternal hypothyroxinemia during gestation altering offspring brain development."
Alan Brown emphasizes that "Although replication in independent studies is required before firm conclusions can be drawn, the study was based on a national birth cohort with a large sample size, increasing the plausibility of the findings."
Adjusting for preterm birth lessened the association between hypothyroxinemia and schizophrenia, suggesting that preterm birth may be contributing to some of the measurably increased risk in the Finnish Maternity Cohort study.
In their paper, published in Biological Psychiatry, authors note that their findings should be studied as a risk factor for other neurodevelopmental disorders as well as schizophrenia — such as bipolar disorder and autism. They hope to stimulate further examinations of how hypothyroxinemia causes neurodevelopmental abnormalities, ultimately contributing to reducing risk of mental illnesses during development.
"This study identifies a preventable potential contributor to the risk for schizophrenia. Maternal hypothyroidism can be easily diagnosed and effectively treated."
John H. Krystal MD, Editor, Biological Psychiatry.
Evidence from animal and human studies indicates that thyroid hormone deficiency during early gestation alters brain development. As schizophrenia is associated with prenatal brain insults and premorbid cognitive deficits, we tested the a priori hypothesis that serologically defined maternal thyroid deficiency during early gestation to mid-gestation is associated with schizophrenia in offspring.
The investigation is based on the Finnish Prenatal Study of Schizophrenia, a nested case-control study that included archived maternal sera from virtually all pregnancies since 1983 (N = >1 million). We identified all offspring in the cohort with a diagnosis of schizophrenia based on the national inpatient and outpatient register and matched them on sex, date of birth, and residence in Finland at time of onset of the case to comparison subjects (1:1) from the cohort. Maternal sera of 1010 case-control pairs were assessed for free thyroxine, and sera of 948 case-control pairs were assessed for thyroid-stimulating hormone.
Maternal hypothyroxinemia (free thyroxine ≤10th percentile, normal thyroid-stimulating hormone) was associated with an increased odds of schizophrenia (odds ratio = 1.75, 95% confidence interval = 1.22–2.50, p = .002). When adjusted for maternal psychiatric history, province of birth, and maternal smoking during pregnancy, the association remained significant (odds ratio = 1.70, 95% confidence interval = 1.13–2.55, p = .010).
In a large, national birth cohort, prospectively documented hypothyroxinemia during early gestation to mid-gestation was associated with increased odds of schizophrenia in offspring. This information can inform translational studies of maternal hypothyroxinemia examining molecular and cellular deviations relevant to schizophrenia.
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